Dietary sodium modulates mRNA abundance of enzymes involved in pituitary processing of proopiomelanocortin.

Dietary sodium modulates mRNA abundance of enzymes involved in pituitary processing of proopiomelanocortin.
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DOI:
10.1023/a:1020746414046
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发表时间:
2001-09-01
期刊:
影响因子:
3.8
通讯作者:
Humphreys, M H
Humphreys, M H
中科院分区:
医学2区
文献类型:
--
作者:
Chandramohan, G;Ni, X P;Humphreys, M H

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在高钠饮食(8%;HSD)下,大鼠垂体神经中间叶(NIL)中原阿片皮质素(POMC)的信使RNA丰度增加,由此产生的利钠多肽-γ-黑素细胞刺激素(Gammy-MSH)的血浆浓度也增加。我们检查了HSD是否也增加了大鼠NIL中前转换酶1和2(PC1,PC2)的mRNA丰度,这两种酶参与了将POMC加工成伽马-MSH的过程。HSD组PC1基因表达在2周后增加40%,3周后增加84%。PC2mRNA在两周后增加40%,三周后增加3倍以上。原位杂交显示PC2的这些结果在1周和2周时仅为零,并伴随着HSD后3周免疫印迹法检测的零PC2蛋白的显著增加。NIL患者PC1和PC2基因丰度的增加与POMC基因表达水平的增加是平行的。LSD组大鼠血浆γ-MSH免疫反应性平均为35.1+/-3.3fmol/ml,但在HSD治疗3周后增加到70.9+/-4.8fmol/ml(P<0.002 vs LSD)。这些结果证实,HSD增加了血浆中γ-MSH的浓度,这与其作为循环利钠肽的作用是一致的。PC1和PC2的NIL表达增加与POMC对HSD的反应平行,表明这些变化是对钠过量状态的协调反应的一部分。
The messenger RNA abundance of proopiome-lanocortin (POMC) is increased in neurointermediate lobe (NIL) of rat pituitary when ingesting a high sodium diet (8%; HSD), as is the plasma concentration of the natriuretic peptide gamma-melanocyte stimulating hormone (gammay-MSH) derived from it. We examined whether the HSD also increases the mRNA abundance in rat NIL of proconvertases 1 and 2 (PC1, PC2), enzymes involved in the processing of POMC into gamma-MSH. PC1 mRNA increased by 40% after two weeks of the HSD and by 84% after three weeks. PC2 mRNA increased by 40% after two weeks and by more than 3 fold after three weeks. These results for PC2 were confined to NIL as shown by in situ hybridization at one and two weeks, and were accompanied by a significant increase in NIL PC2 protein after three weeks of the HSD as measured by immunoblotting. The increases in PC1 and PC2 mRNA abundance were paralleled by an increase in POMC mRNA level in NIL. Plasma gamma-MSH immunoreactivity averaged 35.1 +/- 3.3 fmol/ml in rats on the LSD, but increased to 70.9 +/- 4.8 fmol/ml after 3 weeks of the HSD (p < 0.002 vs LSD). These results confirm that the HSD increases the plasma concentration of gamma-MSH, consistent with a role for it as a circulating natriuretic peptide. The increased NIL expression of PC1 and PC2 in parallel with POMC in response to the HSD suggests that these changes are part of the coordinated response to states of sodium surfeit.